There was a correlation between neuropathology and apoptosis (programmed cell death in the hippocampus of Alzheimer's disease (AD) brains, but no evidence of apoptosis in cells with neurofibrillary tangles (NFTs). The middle and inferior temporal cortices exhibited more mature NFTs than the superior temporal cortex, with this later cortical area demonstrating the greatest number of early tangles. We developed several approaches to elucidating the molecular basis of selective regional vulnerability in AD. Monoclonal antibodies were generated against the entorhinal cortex or basolateral amygdala using the SOFISTIC technique, which labeled subcellular compartments of neurons as well as NFTs. In situ hybridization revealed a deficit in cytochrome oxidase (COX) activity and of messenger RNA (mRNA) expression in association brain regions in AD, in neurons which were stained by an antibody for paired helical filaments (PHF), a constituent of NFTs. Thus neurons expressing PHFs retain some capacity for oxidative phosphorylation. Although senile or neuritic plaques containing Ab-protein did not affect the expression of COX mRNA in neurons adjacent to plaques or of COX enzyme activity around or within these plaques. A brain bank was established to provide appropriate tissue for neuropathological studies in AD. AD patients with clinically identified leukoencephalopathy demonstrated on postmortem exam a severe cortical amyloid angiopathy without involvement of white matter vessels or atherosclerosis.